title: Autophagy is involved in adipogenic differentiation by repressesing proteasome-dependent PPARγ2 degradation.
abstract: Animal studies have shown that autophagy is essential in the process of obesity. Here, we performed daily injection of the autophagy inhibitor chloroquine (CQ) in mice and found that systemic administration of CQ blocks high-fat diet-induced obesity. To investigate the potential underlying molecular mechanism, we employed genetic and pharmacological interventions in cultured preadipocytes to investigate the role of autophagy in the control of the expression of the adipogenic regulator peroxisome proliferatior-activated receptor-γ (PPARγ). We show that adipogenic differentiation of 3T3-L1 preadipocytes is associated with activation of autophagy and increased PPARγ2 protein level. Treatment with CQ, shRNA-mediated knockdown, or genetic engineering-induced deletion of autophagy-related gene 5 (Atg5) promoted proteasome-dependent PPARγ2 degradation and attenuated adipogenic differentiation. Therefore, activated autophagy increases PPARγ2 stability and promotes adipogenic differentiation, and inhibition of autophagy may prevent high-fat diet-induced obesity and the consequential type 2 diabetes.
authors.affiliation: Departments of Medicine, Pharmacology, and Molecular Physiology and Biological Physics and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia;
authors.forename: Chongben
authors.initials: C
authors.lastname: Zhang
authors.forename: Yingke
authors.initials: Y
authors.lastname: He
authors.forename: Mitsuhara
authors.initials: M
authors.lastname: Okutsu
authors.forename: Lai Chun
authors.initials: LC
authors.lastname: Ong
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.forename: Pierce
authors.initials: P
authors.lastname: Chow
authors.forename: Sidney
authors.initials: S
authors.lastname: Yu
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D061988:Proteasome Inhibitors / Q000627:therapeutic use*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability / Q000187:drug effects; D034622:RNA Interference
chemical_list: D019440:Anti-Obesity Agents; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D047495:PPAR gamma; D061988:Proteasome Inhibitors; D020033:Protein Isoforms; D046988:Proteasome Endopeptidase Complex
keywords: adipogenesis; adipogenic differentiation; autophagy; obesity; peroxisome proliferatior-activated receptor-γ2; proteasome-dependent protein degradation